Pretreatment of donor stimulator cells by 16,16 dimethyl prostaglandin E2 influences the recipient immune response.
BACKGROUND
Immunosuppressive strategies have largely ignored donor-derived stimulatory cells as a target. This study examined whether lipopolysaccharide (LPS) or 16,16 dimethyl prostaglandin E2 (dmPGE2) pretreatment of stimulator cells from B10.BR mice influences effector function of responder T lymphocytes from C3H/HeJ mice in vitro or in vivo.


METHODS
B10.BR spleen cells were incubated in vitro in the presence or absence of dmPGE2 or or LPS before the cells were used as stimulators in a mixed lymphocyte culture (MLC) with T cells from C3H/HeJ mice. In parallel studies, B10.BR mice were treated in vivo with dmPGE2 or LPS; spleen cells from these animals were used as stimulators in an MLC and skin was harvested for skin grafts. Cells from untreated or pretreated mice were examined for expression of intercellular adhesion molecule-1 (ICAM-1), B7-1, and B7-2 by fluorescence-activated cell sorter analysis. ICAM-1 mRNA transcripts were determined by reverse transcriptase-polymerase chain reaction.


RESULTS
Stimulation of B10.BR-derived spleen cells with LPS before their use as stimulator cells in a MLC resulted in an increase in responder T-cell proliferation compared with use of unstimulated spleen cells (P < 0.05). In contrast, pretreatment of stimulator spleen cells with dmPGE2 resulted in dose-dependent inhibition of the responder T-cell proliferation, with maximum effect seen using a concentration of dmPGE2 of 10(-5) mol/L. The decreased expression of interleukin-1, tumor necrosis factor, leukotriene B4 procoagulant activity, and ICAM-1 by the dmPGE2 pretreated spleen cells correlated with their inefficient in stimulating T-cell proliferation. Spleen cells harvested from B10.BR mice previously injected with dmPGE2 similarly were inefficient as stimulator cells. Skin graft survival was delayed, but not prevented, by in vivo pretreatment of donor mice with dmPGE2.


CONCLUSIONS
These data demonstrate the effect of immunomodulation of allogeneic stimulator spleen cells on subsequent responder T-lymphocyte function and allograft survival.
Chung
S W
SW
Department of Surgery and Medicine, Vancouver Hospital & Health Sciences Centre, University of British Columbia, Canada.
Gould
B
B
Zhang
R
R
Hu
Y
Y
Levy
G A
GA
Gorczynski
R M
RM
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D006085:Graft Survival / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D008070:Lipopolysaccharides; D015064:16,16-Dimethylprostaglandin E2